Cellular immunity, on the basis of delayed cutaneous hypersensitivity in vivo and the following assays using lymphoid cells from sensitized animals: (1) elaboration of MIF; (2) a proliferative response to antigen; (3) target cell destruction of antigen-coated RBC; can be specifically induced against haptens by immunizing guinea pigs with covalent conjugates of the hapten and mycobacteria. It is proposed to determine if helper activity is also induced by using the hapten to which the animal has developed cellular immunity as a carrier for a second hapten. Such bifunctional antigen molecules have been routinely synthesized in this laboratory during the past several years. The response to hapten-mycobacterial conjugates will be characterized with respect to duration, memory and specificity. It will be determined if immunization with mycobacterial conjugates can surmount genetic barriers, as in the case of the inability of strain of 13 guinea pigs to make a cellular immune response to polylysine. The effectiveness of the method will be assessed in other species. If it is effective in mice, it will be determined if anti-theta sera ablate the response. It is anticipated that the method may provide a general approach to the enhancement of cellular immunity against weakly- or non-immunogenic molecules, including tumor-specific antigens. BIBLIOGRAPHIC REFERENCES: Woods, V., Nitecki, D., and Goodman, J. W.: The Capacity of Bifunctional Antigens to Bridge Antibody Molecules and to Mediate Cell Cooperation. Immunochemistry 12: 379-382,1975. Belldone, C.J. Hanes, D., Nitecki, D.E., and Goodman, J.W.: Role of Macrophages in Immunogenicity of Nonfunctional Antigen. Fed. Proc. 34:958, 1975.